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Cadherin\u20106 (CDH6), an unusual cadherin molecule containing an RGD integrin\u2010binding motif, has multiple functions in the developing nervous system, but whether it contributes to neuronal migration and positioning during neocortical development remains unknown. Here, we investigated the role of CDH6 in the developing cerebral cortex.\n                    <jats:italic>Cdh6<\/jats:italic>\n                    knockdown (KD) using\n                    <jats:italic>in utero<\/jats:italic>\n                    electroporation revealed that CDH6 inhibition caused impaired radial migration and abnormal positioning of neurons. Time\u2010lapse imaging analysis revealed that CDH6 is important for proper neuronal motility. Mechanistically, we show that CDH6 promotes the activation of integrin \u03b21 on migrating neurons. The defect in neuronal migration caused by\n                    <jats:italic>Cdh6<\/jats:italic>\n                    KD was rescued by moderate overexpression of integrin \u03b21 and a KD\u2010resistant form of wild\u2010type CDH6, but not by CDH6 with a mutated RGD motif. These results suggest that CDH6 is required for cortical excitatory neurons to migrate radially by controlling integrin\u2010mediated cell motility.\n                  <\/jats:p>","DOI":"10.1111\/febs.70150","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T23:39:39Z","timestamp":1748475579000},"page":"5382-5397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cadherin\u20106 controls neuronal migration during mouse neocortical development via an integrin\u2010mediated pathway"],"prefix":"10.1111","volume":"292","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9629-0038","authenticated-orcid":false,"given":"Yuki","family":"Hirota","sequence":"first","affiliation":[{"name":"Department of Anatomy Keio University School of Medicine  Tokyo 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